Nutrition support through Parenteral Nutrition (PN) is necessary when patients can not be fed orally, for example when a patient has an impaired GI tract and is unable to tolerate enteral feedings.
PN is a solution that contains fluids, carbohydrates, electrolytes, proteins, amino acids, vitamins; and trace minerals. PN is administered concurrently with an intravenous lipid emulsion that provides essential fatty acids. Commercially available lipid emulsions that are currently used for parenteral use include Intralipid® (Clintec), Liposyn® and Liposyn II® (Abbott Laboratories), Travemusion® (Baxter Healthcare), and Soyacal® (Alpha Therapeutics). These lipid emulsions are composed of a vegetable oil, such as soybean oil or safflower oil, an emulsifying agent such as egg phospholipids, glycerol, and water. Thus, the fatty acid content consists of primarily of the essential omega-6 fatty acids.
The use of PN in patients of all ages has been associated with liver disease, ranging from hepatic steatosis to cirrhosis and ultimately liver failure (1-4, 13-17). Investigators have proposed that it is deficiencies or toxicities of the PN solution that lead to hepatic injury (22-24) and relatively little attention has been given to idea that the lipids delivered with PN pose the problem. In fact, a leading pediatrics textbook, Principles and Practice of Pediatrics, indicates that there is little evidence to suggest that intravenous fat or glucose are associated with the liver disease hepatic cholestasis (Frank A Oski, Deangelis, C D, Feigin R D, McMillan J A, Warshaw, J B, J B lippincott Company 3rd edition: page 1914 (Philadelphia)).
A fish oil based lipid emulsion Omegaven® (Fresenius Kabi), has been developed and used in the European market. Omegaven® is a 10% fish oil emulsion with a high percentage of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosapentaenoic acid (DHA). Simultaneous intravenous administration of Omegaven with a basic lipid emulsion such as Intralipid® provides what is believed to be an optimal ratio of omega-3 to omega-6 fatty acids. The combination of an omega-6 fatty acid lipid emulsion and a seal oil based emulsion, which is rich in omega-3 fatty acids, has also been proposed for use in PN (PCT WO 03/055323).
A study in a newborn pig model showed that intravenous administration of fish oil, which consists of primarily omega-3 fatty acids, reduced parenteral nutrition-induced cholestasis (39). However, the study was only 3 weeks in duration and long-term effects from administration of omega-3 fatty acids alone were not evaluated. In fact, the idea that one could remove an essential fatty acid from the standard regime of nutritional support by PN has not been accepted by those skilled in the art. It is believed that reduction of an essential fatty acid, such as omega-6, during a long-term therapy would clearly result in fatty acid deficiency and deterioration of the health of the patient.
PN associated liver disease is a significant drawback of parenteral nutrition. It presents a severe problem in newborns and infants who are a significant risk of developing chronic liver disease (18, 19). In addition, the prolonged use of PN in children and adults ultimately leads to non-alcoholic fatty liver disease (NAFLD). Thus, there is a need in the art to identify a means for nutritional support that does not lead to such devastating disease.